Perioperative anticoagulation in free microvascular flaps - a comparison of different prophylactic regimes in oncologic reconstructive surgery.

OBJECTIVE: Free tissue transfer has an established place in oncologic head and neck surgery. However, the necessity and specific regimen of perioperative thromboprophylaxis remain controversial. Here, the risk of postoperative hemorrhage contrasts with vascular pedicle thrombosis and graft loss. This work compares three different heparin protocols (A-C) with regard to postoperative complications. PATIENTS AND METHODS: A retrospective analysis of our free flap transplants between 2004 and 2023 was conducted. Inclusion criteria were thromboprophylaxis with (A) 500 IU/h unfractionated heparin (UFH), (B) low-molecular-weight heparin (LMWH) once daily, and (C) LMWH once daily with additional immediate preoperative administration. Primary endpoints were the incidence of postoperative bleeding and hematoma and the appearance of flap thrombosis. RESULTS: We evaluated 355 cases, 87 in group A, 179 in group B, and in group C 89 patients. Overall, postoperative bleeding occurred in 8.7% of patients, and 83% underwent hemostasis under intubation anesthesia, with no significant difference between groups (p = 0.784). Hematoma formation requiring revision was found in 3.7% of patients (p = 0.660). We identified postoperative hematoma as a significant influencing factor for venous pedicle thrombosis (OR 3.602; p = 0.001). Venous and arterial flap thrombosis in the graft vessel showed no difference between the groups (p = 0.745 and p = 0.128). CONCLUSIONS: The three anticoagulation regimens appear to be equivalent therapy for the prevention of thrombosis without significant differences in postoperative bleeding. The use of LMWH with additional preoperative administration can, therefore, be administered in free flap reconstruction.

Predictive factors for abscessing tonsillitis: a retrospective analysis.

OBJECTIVE: In clinical practice, identifying abscesses in tonsillar infections is crucial for early therapeutic management. Diagnosis of a peritonsillar abscess is usually based on clinical symptoms. Complementary examination procedures, such as laboratory parameters and imaging, are available for confirmation. PATIENTS AND METHODS: A retrospective analysis was carried out of data for 752 patients who presented with acute tonsillar infection and were hospitalized between January 2012 and February 2021. The data analyses involved evaluating the patient's clinical symptoms, inflammatory parameters, and previous medical history in relation to the predictive power of these factors for the presence of an abscess. RESULTS: Predictor analysis for the presence of an abscess showed significant values for trismus (OR 2.392; 95% CI, 1.305 to 4.383; p=0.005) and palatal arch protrusion (OR 29.679; 95% CI, 17.460 to 50.447; p=0.000). The inflammatory parameter C-reactive protein and the leukocyte count were not statistically significant as predictors. CONCLUSIONS: The presence of a tonsillar abscess can be diagnosed from the clinical presentation alone if the findings are clear. Further diagnostic procedures are indicated in case of inconclusive findings, and ultrasound should be the primary noninvasive method. Computed tomography is only required in selected cases. Inflammatory parameters can be assessed in order to monitor therapy, but do not predict the presence of an abscess. However, if defined action sequences are being considered, tonsillar abscesses can be differentiated at an early point.

EAONO/JOS classification for acquired cholesteatoma: evaluating the impact of the number of affected sites on treatment and outcomes.

PURPOSE: The European and Japanese system for cholesteatoma classification proposed an anatomical differentiation in five sites. In stage I disease, one site would be affected and in stage II, two to five. We tested the significance of this differentiation by analyzing the influence of the number of affected sites on residual disease, hearing ability and surgical complexity. METHODS: Cases of acquired cholesteatoma treated at a single tertiary referral center between 2010-01-01 and 2019-07-31 were retrospectively analyzed. Residual disease was determined according to the system. The air-bone gap mean of 0.5, 1, 2, 3 kHz (ABG) and its change with surgery served as hearing outcome. The surgical complexity was estimated regarding the Wullstein's tympanoplasty classification and the procedure approach (transcanal, canal up/down). RESULTS: 513 ears (431 patients) were followed-up during 21.6 ± 21.5 months. 107 (20.9%) ears had one site affected, 130 (25.3%) two, 157 (30.6%) three, 72 (14.0%) four and 47 (9.2%) five. An increasing number of affected sites resulted in higher residual rates (9.4-21.3%, p = 0.008) and surgical complexity, as well poorer ABG (preoperative 14.1 to 25.3 dB, postoperative 11.3-16.8 dB, p < 0.001). These differences existed between the means of cases of stage I and II, but also when only considering ears with stage II classification. CONCLUSION: The data showed statistically significant differences when comparing the averages of ears with two to five affected sites, questioning the pertinence of the differentiation between stages I and II.

The COVID-19 pandemic and its consequences for the diagnosis and therapy of head and neck malignancies.

OBJECTIVE: The COVID-19 pandemic and the measures accompanying it have been accused of having a negative influence on the frequency and methods of treatment of various diseases including head and neck cancer (HNSCC). To go further into this assumption, the diagnoses made, and treatments performed at one of Germany's largest head and neck cancer centres were evaluated. PATIENTS AND METHODS: This study consisted of one single centre and involved a retrospective review of all patients with newly diagnosed or recurrent HNSCC. The diagnosis and treatment methods used in the pre-COVID-19 time period between March 1st, 2019, and March 1st, 2020, were analysed and compared with the COVID-19 time period from April 1st, 2020, until April 1st, 2021. The primary objective was defined as the number of malignant diagnoses and the secondary objectives as the disease stage and the time to therapy. RESULTS: A total of 612 patients (160♀; mean 63 yrs.) were included. 319 patients (52%) were treated in the pre-COVID-19 time. The two groups did not differ in terms of age (p=0.304), gender (p=0.941), presence of recurrent disease (p=0.866), tumour subsite (p=0.194) or the duration from presentation to the multidisciplinary tumour board until start of therapy (p=0.202). There were no significant differences in the T stage (p=0.777), N stage (p=0.067) or UICC stage (p=0.922). During the pre-COVID-19 period more patients presented with distant metastases (n= 23 vs. n=8; p=0.011). CONCLUSIONS: This study shows that there was no significant change in either the number and severity of HNSCC diagnoses or the time until start of therapy at this large head and neck cancer centre as a result of the COVID-19 pandemic.

Topological Alterations of the Structural Brain Connectivity Network in Children with Juvenile Neuronal Ceroid Lipofuscinosis.

BACKGROUND AND PURPOSE: We used diffusion MR imaging to investigate the structural brain connectivity networks in juvenile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease of childhood. Although changes in conventional MR imaging are typically not visually apparent in children aged <10 years, we previously found significant microstructural abnormalities by using diffusion MR imaging. Therefore, we hypothesized that the structural connectivity networks would also be affected in the disease. MATERIALS AND METHODS: We acquired diffusion MR imaging data from 14 children with juvenile neuronal ceroid lipofuscinosis (mean ± SD age, 9.6 ± 3.4 years; 10 boys) and 14 control subjects (mean ± SD age, 11.2 ± 2.3 years; 7 boys). A follow-up MR imaging was performed for 12 of the patients (mean ± SD age, 11.4 ± 3.2 years; 8 boys). We used graph theoretical analysis to investigate the global and local properties of the structural brain connectivity networks reconstructed with constrained spherical deconvolution-based whole-brain probabilistic tractography. RESULTS: We found significantly increased characteristic path length (P = .003) and decreased degree (P = .003), which indicated decreased network integration and centrality in children with juvenile neuronal ceroid lipofuscinosis. The findings were similar for the follow-up MR imaging, and there were no significant differences between the two acquisitions of the patients. In addition, we found that the disease severity correlated negatively (P < .007) with integration, segregation, centrality, and small-worldness of the networks. Moreover, we found significantly (P < .0003) decreased local efficiency in the left supramarginal gyrus and temporal plane, and decreased strength in the right lingual gyrus. CONCLUSIONS: We found significant global and local network alterations in juvenile neuronal ceroid lipofuscinosis that correlated with the disease severity and in areas related to the symptomatology.

Analysis of smoking behaviour in patients with peritonsillar abscess: a prospective, matched case-control study.

OBJECTIVE: Smoking is purported to increase the risk of peritonsillar abscess formation, but prospective data are needed to confirm this hypothesis. This prospective study aimed to identify this correlation. METHODS: Fifty-four patients with peritonsillar abscess were prospectively asked about their smoking behaviour using a questionnaire that was designed and approved by the Robert Koch Institute (Berlin, Germany) to analyse smoking behaviour in epidemiological studies. Afterwards, a consecutive control group (without peritonsillar abscess), matched in terms of age and gender, was surveyed using the same questionnaire. A classification of smoker, former smoker and non-smoker was made, and the numbers of pack-years were calculated and compared. RESULTS: Statistical analysis of both groups revealed a significant correlation between peritonsillar abscess and smoking experience (p = 0.025). Moreover, there were significantly fewer non-smokers in the non-peritonsillar abscess group (p = 0.04). The number of pack-years was higher in the peritonsillar abscess group (p = 0.037). CONCLUSION: There is a statistically significant association between peritonsillar abscess and smoking.

Global and Widespread Local White Matter Abnormalities in Juvenile Neuronal Ceroid Lipofuscinosis.

BACKGROUND AND PURPOSE: Juvenile neuronal ceroid lipofuscinosis is a progressive neurodegenerative lysosomal storage disease of childhood. It manifests with loss of vision, seizures, and loss of cognitive and motor functions leading to premature death. Previous MR imaging studies have reported cerebral and cerebellar atrophy, progressive hippocampal atrophy, thalamic signal intensity alterations, and decreased white matter volume in the corona radiata. However, conventional MR imaging findings are usually normal at younger than 10 years of age. The purpose of our study was to investigate whether diffusion MR imaging could reveal changes in white matter microstructure already present at a younger age. MATERIALS AND METHODS: We investigated global and local white matter abnormalities in 14 children with juvenile neuronal ceroid lipofuscinosis (mean age, 9.6 ± 3.4 years; 10 boys) and 14 control subjects (mean age, 11.2 ± 2.3 years; 7 boys). Twelve patients underwent follow-up MR imaging after 2 years (mean age, 11.4 ± 3.2 years; 8 boys). We performed a global analysis using 2 approaches: white matter tract skeleton and constrained spherical deconvolution-based whole-brain tractography. Then, we investigated local microstructural abnormalities using Tract-Based Spatial Statistics. RESULTS: We found globally decreased anisotropy (P = .000001) and increased diffusivity (P = .001) in patients with juvenile neuronal ceroid lipofuscinosis. In addition, we found widespread increased diffusivity and decreased anisotropy in, for example, the corona radiata (P < .001) and posterior thalamic radiation (P < .001). However, we found no differences between the first and second acquisitions. CONCLUSIONS: The patients with juvenile neuronal ceroid lipofuscinosis exhibited global and local abnormalities in white matter microstructure. Future studies could apply more specific microstructural models and study whether these abnormalities are already present at a younger age.

Docetaxel chemotherapy in metastatic castration-resistant prostate cancer: cost of care in Medicare and commercial populations.

OBJECTIVE: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: This study used the Medicare 5% sample and MarketScan Commercial (2010-2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date. Docetaxel drug claim costs were adjusted for 2011 generic docetaxel introduction, while other costs were adjusted to 2015 values using the national average annual unit cost increase. RESULTS: This study identified 281 Medicare-insured and 155 commercially insured men, with 325 and 172 docetaxel episodes, respectively. The average number of cycles (unique docetaxel infusion days) per episode was 6.9 for Medicare and 6.3 for commercial cohorts. The average cost per episode was $28,792 for Medicare and $67,958 for commercial cohorts, with docetaxel drug costs contributing $2,588 and $13,169 per episode, respectively. The average cost per episode on docetaxel infusion days was $8,577 (30%) for Medicare and $28,412 (42%) for commercial. Non-docetaxel infusion day costs included $7,074 (25%) for infused or injected drugs for Medicare, $10,838 (16%) for commercial cohorts, and $6,875 (24%) and $9,324 (14%) for inpatient admissions, respectively. LIMITATIONS: The applicability is only to the metastatic castration-resistance clinical setting, rather than the metastatic hormone-sensitive setting, and the lack of data on the cost effectiveness of different sequencing strategies of a range of systemic therapies including enzalutamide, abiraterone, radium-223, and taxane chemotherapy. CONCLUSION: The majority of docetaxel episode costs in Medicare and commercial mCRPC populations were non-docetaxel drug costs. Future research should evaluate the total cost of care in mCPRC.

Plant genotype and nitrogen loading influence seagrass productivity, biochemistry, and plant-herbivore interactions.

Genetic variation within and among key species can have significant ecological consequences at the population, community, and ecosystem levels. In order to understand ecological properties of systems based on habitat-forming clonal plants, it is crucial to clarify which traits vary among plant genotypes and how they influence ecological processes, and to assess their relative contribution to ecosystem functioning in comparison to other factors. Here we used a mesocosm experiment to examine the relative influence of genotypic identity and extreme levels of nitrogen loading on traits that affect ecological processes (at the population, community, and ecosystem levels) for Zostera marina, a widespread marine angiosperm that forms monospecific meadows throughout coastal areas in the Northern Hemisphere. We found effects of both genotype and nitrogen addition on many plant characteristics (e.g., aboveground and belowground biomass), and these were generally strong and similar in magnitude, whereas interactive effects were rare. Genotypes also strongly differed in susceptibility to herbivorous isopods, with isopod preference among genotypes generally matching their performance in terms of growth and survival. Chemical rather than structural differences among genotypes drove these differences in seagrass palatability. Nitrogen addition uniformly decreased plant palatability but did not greatly alter the relative preferences of herbivores among genotypes, indicating that genotype effects are strong. Our results highlight that differences in key traits among genotypes of habitat-forming species can have important consequences for the communities and ecosystems that depend on them and that such effects are not overwhelmed by known environmental stressors.

LPS differentially affects vasoconstrictor responses: a potential role for RGS16?

The profound hypotension in septic shock patients is difficult to treat as it is accompanied by depressed constrictor responses to alpha1-adrenoceptor agonists. Bacterial lipopolysaccharide (LPS) is the main trigger for most of the cardiovascular alterations occurring in septic shock. In this study we investigated the effects of LPS exposure on vascular contractility in general and the role of Regulator of G protein Signalling (RGS) proteins in the LPS-induced vascular alterations. Exposure of rat aortic rings to various LPS concentrations (3, 10, 30 microg/ml) for 22 hours differentially affected agonist-induced contractile responses at four distinct G-protein coupled receptors (alpha1-adrenoceptors, angiotensin II, serotonin and endothelin-1 receptors). While the endothelin-1-induced contraction was unaffected by LPS pre-treatment, phenylephrine- and angiotensin II-induced contraction were significantly reduced whereas serotonin-induced contraction was significantly enhanced. Concomitantly, LPS treatment increased the RGS16 mRNA expression both in aortic rings and cultured vascular smooth muscle cells (VSMCs) but not that of RGS2, RGS3, RGS4 or RGS5. The significant increase in RGS16 mRNA expression in VSMCs by LPS was time- and concentration-dependent but independent of increased inducible NO synthase (iNOS) activity. The changes in RGS16 mRNA might contribute to the differential regulation of the contractile responses to vasoconstrictors upon LPS exposure.

BML-241 fails to display selective antagonism at the sphingosine-1-phosphate receptor, S1P(3).

BACKGROUND AND PURPOSE: The thiazolidine carboxylic acid, BML-241, has been proposed as a lead compound in development of selective antagonists at the sphingosine-1-phosphate receptor (S1P3), based on its inhibition of the rise in intracellular calcium concentrations ([Ca2+]i) in HeLa cells overexpressing S1P receptors. We have studied the antagonistic properties of BML-241 for the S1P(3) receptor in more detail. EXPERIMENTAL APPROACH: Chinese hamster ovary (CHO) cells stably transfected with the S1P3, S1P2 or alpha(1A)-adrenoceptors were used to investigate the effect of BML-241 on increases in [Ca2+]i mediated via different receptors. CHO-K1 cells were used to study ATP-induced [Ca2+]i elevations. Effects on S1P3 -mediated inhibition of forskolin-induced cAMP accumulation and on binding to alpha(1A)-adrenoceptors were also investigated. In addition, the effect of BML-241 on contractions of rat mesenteric artery induced by phenylephrine was studied in an organ bath. KEY RESULTS: High concentrations of BML-241 (10 microM) inhibited the rise in [Ca2+]i induced by S1P3 and S1P2 receptor stimulation; lower concentrations were ineffective. This high concentration of BML-241 also inhibited [Ca2+]i increases via P2 (nucleotide) receptor or alpha(1A)-adrenoceptor stimulation. Moreover, BML-241 (10 microM) inhibited alpha(1)-adrenoceptor-mediated contraction of rat mesenteric artery but did not displace [3H]-prazosin from alpha(1A)-adrenoceptors in concentrations up to 100 microM. BML-241 (10 microM) did not affect the S1P3 -mediated decrease of forskolin-induced cAMP accumulation. CONCLUSIONS AND IMPLICATIONS: We conclude that BML-241 is a low potency, non-selective inhibitor of increases in [Ca2+]i, rather than a specific antagonist at the S1P3 receptor.

The role of free oxygen radicals in the aetiopathogenesis of rosacea.

A possible link between superoxide dismutase activity and malondialdehyde level with the clinical manifestations of rosacea was investigated. We found differences in superoxide dismutase activities between mild rosacea (stages I and II) and severe involvement (stage III) groups, as well as between disease and control groups that were statistically significant (P < 0.05). In the mild involvement group (stages I and II), the superoxide dismutase activity was higher than in the control group (P < 0.05), while the malondialdehyde levels did not differ from the control. In the severe involvement group (stage III), the superoxide dismutase activity was lower than in the control group (P < 0.05), and this was coupled to a raised level of malondialdehyde (P < 0.05). These findings clearly show that in the mild involvement phase of rosacea patients, superoxide dismutase activity was stimulated to protect the skin against reactive oxygen species so that the malondialdehyde levels were maintained. In contrast, in more severe disease, due to a decrease in the capacity of the antioxidant defence system, the malondialdehyde levels were increased. These findings support the 'antioxidant system defect hypothesis' in rosacea patients.

Fermented wheat in liquid diets: effects on gastrointestinal characteristics in weanling piglets.

Effects of adding fermented wheat to liquid diets on gastrointestinal characteristics in weanling piglets were studied. Gastrointestinal characteristics of 40 28-d-old weanling piglets were measured at the day of weaning (d 0) and at d 4 and 8 after weaning. Piglets were group-housed and fed twice daily. Feeding level was based on the average metabolic BW of piglets per group. Groups were fed a liquid diet with either 45% unfermented wheat (FERM_0) or 45% fermented wheat (FERM_45). The other 55% of the diet was identical. To ferment wheat, water at 30 degrees C was added to milled wheat in a 1:2.2 ratio. The pH and contents of lactic acid, acetic acid, propionic acid, and butyric acid were measured in the digesta of the stomach, three parts of the small intestine, cecum, and large intestine. In addition, changes in microbial populations in the digesta were studied during the period after weaning. Moreover, villus height, crypt depth, and villus shape were studied in the small intestine. Piglets fed FERM_45 showed lower gastric pH (P < 0.05) at d 4 and higher gastric lactic acid content (P < 0.001) at both d 4 and 8. Piglets fed FERM_45 showed in the first part of the small intestine higher villus height (P < 0.01) at d 8 and higher villus:crypt ratio (P < 0.001) at both d 4 and 8. Villus shape tended (P < 0.10) to be favorable for piglets fed FERM_45. The present study indicates that feeding a partly fermented liquid diet to weanling piglets may be a concept to prevent undesirable changes in mucosal architecture after weaning.

Elucidation of the pathways of catabolic glutamate conversion in three thermophilic anaerobic bacteria.

The glutamate catabolism of three thermophilic syntrophic anaerobes was compared based on the combined use of [(13)C] glutamate NMR measurements and enzyme activity determinations. In some cases the uptake of intermediates from different pathways was studied. The three organisms, Caloramator coolhaasii, Thermanaerovibrio acidaminovorans and strain TGO, had a different stoichiometry of glutamate conversion and were dependent on the presence of a hydrogen scavenger (Methanobacterium thermoautotrophicum Z245) to a different degree for their growth. C. coolhaasii formed acetate, CO(2), NH(4)(+) and H(2) from glutamate. Acetate was found to be formed through the beta-methylaspartate pathway in pure culture as well as in coculture. T. acidaminovorans converted glutamate to acetate, propionate, CO(2), NH(4)(+) and H(2). Most likely, this organism uses the beta-methylaspartate pathway for acetate formation. Propionate formation occurred through a direct oxidation of glutamate via succinyl-CoA and methylmalonyl-CoA. The metabolism of T. acidaminovorans shifted in favour of propionate formation when grown in coculture with the methanogen, but this did not lead to the use of a different glutamate degradation pathway. Strain TGO, an obligate syntrophic glutamate-degrading organism, formed propionate, traces of succinate, CO(2), NH(4)(+) and H(2). Glutamate was converted to propionate oxidatively via the intermediates succinyl-CoA and methylmalonyl-CoA. A minor part of the succinyl-CoA was converted to succinate and excreted.

Phenotypic effects of leptin in an ectotherm: a new tool to study the evolution of life histories and endothermy?

Leptin is a hormone that regulates energy expenditure and body mass in mammals, and it has attracted considerable attention because of its potential in treating human obesity. Comprehensive data from both pathological and non-pathological systems strongly support a role for leptin in regulating energy metabolism, in thermoregulation and in regulating the onset of puberty. We report here that daily injections of recombinant murine leptin in fence lizards (Sceloporus undulatus) produce phenotypic effects similar to those observed when leptin injections are given to mice. Lizards injected with leptin had body temperatures 0.6 degrees C higher, ate 30 % less food and showed a 14 % reduction in activity rates, and females showed a 2. 5-fold increase in resting metabolic rates, compared with lizards injected with vehicle only (phosphate-buffered saline). We also detected native lizard leptin using an immunoassay. Our results indicate that leptin is expressed in ectotherms and may be conserved both functionally and structurally. In the wake of unprecedented research activity on the role of leptin as a cause of, and potential treatment for, human obesity, we believe that other applications of leptin research have been ignored. For example, the response of lizards to leptin injection in our study has important implications for two broad areas of research in evolutionary biology: the evolution of age at first reproduction and of endothermy. We argue that research in these areas, previously limited to comparative approaches, may now benefit from experimental manipulations using leptin.

Transient neurological symptoms after spinal anaesthesia with hyperbaric 5% lidocaine or general anaesthesia.

Transient neurotoxicity of concentrated local anaesthetics has been thought to be the main reason for transient neurological symptoms after spinal anaesthesia. Profound musculoligamental relaxation by high doses of local anaesthetics may contribute to the development of postoperative musculoskeletal pain. In order to evaluate the role of the loss of strength of the supportive structures of the spine in the development of transient neurological symptoms, 60 patients (ASA I-II) undergoing minor orthopaedic, varicose vein or inguinal hernia operations were allocated randomly to receive spinal anaesthesia with hyperbaric lidocaine 50 mg ml-1 (85-100 mg) or balanced general anaesthesia with neuromuscular block. Patients were interviewed 24 h later and after 1 week they returned a written questionnaire. Transient neurological symptoms, consisting of pain in the buttocks or pain radiating symmetrically to the lower extremities, occurred in eight patients (27%) receiving spinal anaesthesia and in one patient (3%) receiving general anaesthesia (P < 0.05). We conclude that a transient neurotoxic effect of hyperbaric lidocaine 50 mg ml-1 is probably the main reason for transient neurological symptoms after spinal anaesthesia but musculoligamental relaxation may contribute to the development of low back or leg pain after both anaesthetic techniques.

Red cell lipid peroxidation and antioxidant system in haemodialysed patients: influence of recombinant human erythropoietin (r-HuEPO) treatment.

In order to determine the role of correcting anaemia with r-HuEPO on susceptibility of red cell to lipid peroxidation, 15 patients on maintenance haemodialysis treated with r-HuEPO for at least one year (group I), 15 patients on maintenance haemodialysis without r-HuEPO (group II) and 30 persons as a control group (group III) were included in the study. We measured erythrocyte superoxide dismutase (e-SOD), erythrocyte catalase (e-CAT) activities, plasma malonyldialdehyde (p-MDA) and serum vitamin E levels in all patients. The healthy controls (group III) had significantly lower levels of p-MDA in comparison to those measured in haemodialysed patients (group I-II) (p < 0.0001). e-SOD activity in group III was significantly higher than in groups I and II, respectively (p < 0.0001 and p < 0.00001), and e-SOD activity was significantly lower in group II than in group I (p < 0.0001). e-CAT activity in group III was higher than in groups I and II, respectively (p < 0.0001 and p < 0.00001) and it was significantly lower in group II than in group I (p < 0.0001). Vitamin E concentration in group III was lower than in group I and group II, respectively (p < 0.0001 and p < 0.0001). But there is no difference between groups I and II. This study suggests that r-HuEPO therapy improves anaemia by decreasing lipid peroxidation and increasing antioxidant activity.

Effect of rhBMP-2 on the osteogenic potential of bone marrow stromal cells from an osteogenesis imperfecta mouse (oim).

To understand whether osteogenesis imperfecta (OI) could result from defective differentiation of osteoprogenitor cells, we investigated the osteogenic potential of bone marrow stromal cells from a mouse model of human OI (oim). Bone marrow was flushed from the femurs and tibias of oim and normal littermates using a syringe with Dulbecco's modified Eagle's medium, and cells were allowed to adhere to flasks. Adherent cells were trypsinized and passaged weekly at a 1:4 split. The established stromal cells were assessed for collagen synthesis, alkaline phosphatase, and osteocalcin production in the presence or absence of rhBMP-2. The stromal cells were also assessed for mineralization by Von-Kossa staining and for exogenous gene transfer using adeno-lacZ and a retroviral vector. The bone marrow stromal cells from oim mice synthesized alpha 1(I) homotrimers as expected, whereas the stromal cells from the normal littermates synthesized alpha 1(I)2 alpha 2(I) heterotrimers. The bone marrow stromal cells exhibited low levels of alkaline phosphatase activity under basal conditions: upon treatment with rhBMP-2, the level of the alkaline phosphatase activity increased approximately 40-fold. Cytochemical staining of the cells confirmed the expression of alkaline phosphatase by the oim stromal cells and its augmentation by rhBMP-2. Osteocalcin production in the stromal cells was also enhanced approximately threefold by rhBMP-2. oim stromal cells grown in the presence of beta-glycerophosphate and ascorbic acid demonstrated Von-Kossa-positive solid deposits after 3 weeks in culture. Ten days after infection with adeno-lacZ, approximately 70% of oim stromal cells expressed the transgene product, and after infection with a retrovirus, approximately 20% of the cells expressed the transgene. These data indicate that bone marrow stromal cells, have osteogenic potential, and also the potential to be transduced with exogenous genes. Under basal conditions, however, the stromal cells from oim mice exhibited significantly lower levels of alkaline phosphatase activity than their normal littermates.

The role of reactive oxygen metabolites in ulcerative colitis.

SUMMARY: : Reactive oxygen metabolites (ROMs) contribute to tissue injury in inflammatory bowel disease. The aim of this study is to examine the role of ROMs in the tissue injury in ulcerative colitis (UC). The study group consisted of 27 patients with UC (14 active, 13 quiescent) and a control group of 10 patients with various anal diseases. We measured the content of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO) in colorectal biopsies. MDA was measured by the thiobarbituric acid assay. SOD and MPO were measured using the nitro blue tetrazolium and odianisidine methods, respectively. The MDA, SOD, and MPO tissue levels were significantly different between the patients with active UC, the patients with quiescent UC, and the control subjects (p < 0.001). A positive correlation was found between the tissue concentrations of MDA and MPO and the activity of the disease (p < 0.001). The SOD tissue concentrations were negatively correlated with the disease activity (r = -0.507, p < 0.05).

Measurement of coronary artery calcium with dual-slice helical CT compared with coronary angiography: evaluation of CT scoring methods, interobserver variations, and reproducibility.

OBJECTIVE: This study was performed to evaluate new scoring methods for quantitating coronary artery calcifications with helical CT and to compare the results with those of quantitative coronary angiography in patients with suspected coronary artery disease. SUBJECTS AND METHODS: Unenhanced dual-slice helical CT and coronary angiography were performed within 24 hr of each other in 101 patients with symptoms of coronary artery disease. Coronary artery calcifications with a density above 90 H were identified on each slice and, with the same regions of interest, quantitative scoring was performed at thresholds of 90 H (new) 130 H (old). Two mathematical algorithms (one new and one old) were evaluated for both thresholds (yielding four scoring systems). By CT imaging, we defined disease as a score of greater than zero. By angiography, we defined disease as a 50% or greater reduction in the luminal diameter of any major vessel. Interobserver variations in calcification scoring were evaluated. Seventeen of our patients. also underwent a second, consecutive CT scan to determine reproducibility. RESULTS: With the new threshold and the new algorithm, the sensitivity, specificity, and accuracy of helical CT in predicting disease were 88%, 52%, and 76%, respectively. We found a moderate positive association between the total CT calcification score and the number of stenotic coronary arteries at angiography (Pearson's correlation coefficient, .43; p = .05 [analysis of variance]). The accuracy and the area under the receiver operating characteristic curve were higher with the new threshold and the new algorithm. Interobserver agreement in calcification scoring was high (intraclass correlation coefficient, .99 [n = 85]), as was reproducibility (intraclass correlation coefficient, .94 [n = 17]). Reproducibility was higher when scoring was based on the new threshold and the new algorithm. CONCLUSION: The quantity of coronary artery calcifications as measured by helical CT correlated positively with obstructive coronary artery disease as measured by angiography. Interobserver agreement and reproducibility were excellent. A new scoring method showed promise.